Role of Antibody-Mediated Tumor Targeting and Route of Administration in Nanoparticle Tumor Accumulation in Vivo

Abstract

In this study, we have looked at enhancing tumor uptake and intracellular delivery of gold nanoparticles (AuNPs) while reducing the systemic exposure by systematic evaluation of the impact of targeting and route of administration on organ distribution. High-resolution microSPECT/CT imaging was used to track the in vivo fate of (111)In-labeled nontargeted and human epidermal growth factor receptor-2 (HER-2) targeted AuNPs following intravenous (i.v.) or intratumoral (i.t.) injection. For i.v. injection, the effects of GdCl3 (for deactivation of macrophages) and nonspecific (anti-CD20) antibody rituximab (for blocking of Fc mediated liver and spleen uptake) were studied. It was found that HER-2 targeting via attachment of trastuzumab paradoxically decreased tumor uptake as a result of faster elimination of the targeted AuNPs from the blood while improving internalization in HER-2-positive tumor cells as compared to nontargeted AuNPs. I.T. injections with HER-2 targeted AuNPs resulted in high tumor retention with low systemic exposure and represents an attractive delivery strategy. Our results provide a strategy for optimizing tumor delivery and quantifying organ distribution of this widely studied class of nanomaterial.

Intratumorally Injected 177Lu-Labeled Gold Nanoparticles: Gold Nanoseed Brachytherapy with Application for Neoadjuvant Treatment of Locally Advanced Breast Cancer

“…The slow elimination of gold nanoseeds from the tumors was due to the properties of AuNP, which result in tumor retention after intratumoral injection (24). We previously found that 111 In-labeled AuNP modified with trastuzumab to target human epidermal growth factor receptor 2 was similarly retained by MDA-MB-361 human BC xenografts in mice after intratumoral injection, whereas intravenously injected AuNP were sequestered by the liver, spleen, and kidneys, greatly diminishing their tumor localization (24). OPSS-PEG-DOTA-177 Lu polymer not linked to AuNP injected intratumorally was ineffective for preventing tumor growth (Fig.…”

Passive versus Active Tumor Targeting Using RGD- and NGR-Modified Polymeric Nanomedicines

“…This, together with the fact that I) the intratumoral penetration of nanomaterials with sizes exceeding ~10 nm tends to be poor [32][33][34] and that II) the presence of targeting ligands on the surface of nanocarriers generally has deleterious pharmacokinetic consequences (reducing their circulation half-life times and their passive EPR-mediated accumulation in tumors 11,27,29 ), calls for a systematic analysis of the benefit of active versus passive tumor targeting. Surely, under certain circumstances, e.g.…”

A new target ligand Ser–Glu for PEPT1-overexpressing cancer imaging

“…[6][7][8] Although many ligands demonstrate highly specific targeting ability in vitro, only a small number of them practically enhance the tumor accumulation of systemically administered NPs. [9][10][11][12][13][14][15] This limitation has inspired attempts to develop ligands for tumor-targeted applications with high efficiency.…”